Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor r Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
- Author(s)
- Kwi-Hyun Bae; Jung Beom Seo; Hye-Young Seo; Sun Hee Kang; Hui-Jeon Jeon; Jae Man Lee; Sungwoo Lee; Jung-Guk Kim; In-Kyu Lee; Gwon-Soo Jung; Keun-Gyu Park; Yun-A Jung
- Keimyung Author(s)
- Kang, Sun Hee
- Department
- Dept. of Internal Medicine (내과학)
- Journal Title
- Endocrinology and Metabolism
- Issued Date
- 2017
- Volume
- 32
- Issue
- 1
- Keyword
- Renal tubulointerstitial fibrosis; Lobeglitazone; Transforming growth factor beta; Unilateral ureteral obstruction
- Abstract
- Background: Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease.
Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy,
much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone,
a novel PPARγ agonist, on renal fibrosis in mice.
Methods: We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced
renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in
renal tubulointerstitial fibrosis through in vivo and in vitro study.
Results: Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal
atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction
and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation,
α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial
cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by
inhibition of the TGF-β/Smad signaling pathway.
Conclusion: The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting
that its clinical applications could extend to the treatment of non-diabetic origin renal disease.
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